N(Me2)Val-Val-N(Me)Val-Pro-OH | 134816-29-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N(Me2)Val-Val-N(Me)Val-Pro-OH
• 英文别名: (2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methylbutanoyl]pyrrolidine-2-carboxylic acid
• CAS: 134816-29-8
• 化学式: C₂₃H₄₂N₄O₅
• 分子量: 454.61
• InChiKey: VCNFUJVIIAGOIO-VJANTYMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N(Me2)Val-Val-N(Me)Val-Pro-OH 、 在 N-羟基-7-氮杂苯并三氮唑 、 2-Chloro-1,3-dimethylimidazolidinium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以84%的产率得到dolastatin 15
  参考文献：
  名称：

  Convergent Synthesis of Dolastatin 15 by Solid Phase Coupling of an N-Methylamino Acid

  摘要：

  Convergent synthesis of dolastatin 15 (1), a cytostatic depsipeptide isolated from the Indian Ocean sea hare, has been described. For construction of the backbone, a single-step condensation of peptide fragment 2 and pyrrolidone fragment 3 was successfully performed using 2-chloro-1,3-dimethyl-2-imidazolinium hexafluorophosphate (CIP) developed by us as an efficient coupling reagent. Coupling of an N-methylamino acid on solid support was first achieved using CTP for the efficient synthesis of peptide fragment 2. The effectiveness of CIP for the coupling of N-methylamino acids in solution and on solid support were clarified by the syntheses of model di- and tripeptides.

  DOI：

  10.1021/jo981055a
• 作为产物：
  描述：

  N-苄氧羰基-N-甲基-L-缬氨酸 在 10% palladium on active carbon N-甲基吗啉 、 sodium hydroxide 、 氰基磷酸二乙酯 、 氢气 、 三甲基乙酰氯 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 水 为溶剂， 生成 N(Me2)Val-Val-N(Me)Val-Pro-OH
  参考文献：
  名称：

  Pettit, George R.; Herald, Delbert L.; Singh, Sheo Bux, Journal of the American Chemical Society, 1991, vol. 113, # 17, p. 6692 - 6693

  摘要：

  DOI：

文献信息

• Synthesis and Biological Activity of Chimeric Structures Derived from the Cytotoxic Natural Compounds Dolastatin 10 and Dolastatin 15
  作者：Joël Poncet、Magali Busquet、Florence Roux、Alain Pierré、Ghanem Atassi、Patrick Jouin

  DOI：10.1021/jm970800t

  日期：1998.4.1

  The natural cytotoxic compounds dolastatins 10 and 15 exhibit great similarities in structure and in their biological activity profiles. Two compounds (1 and 2) formed by interchanging the dolaisoleuine residue of dolastatin 10 and the MeVal-Pro dipeptide of dolastatin 15 were synthesized in order to evaluate the possible equivalence of these units. These compounds can be considered as chimeras of dolastatins 10 and 15 formed by the N-terminal part of the former and the C-terminal part of the latter and vice versa. Both analogues exhibited a marked decrease in their cytotoxic activity but showed similar differential cytotoxicity with regard to the cell Lines assayed compared with the parent compounds. HT-29 cell line was the least sensitive one. However, this activity was in the nanomolar level and close to that of vincristine. The differences in their effect on tubulin polymerization were less pronounced. We confirmed the already known crucial role of the Dil residue in this assay. The nonequivalence of the Dil unit and the MeVal-Pro dipeptide probably reflects modification in the relative positions of the N-dimethylamino and the phenyl moieties.
• Convergent Synthesis of Dolastatin 15 by Solid Phase Coupling of an <i>N</i>-Methylamino Acid
  作者：Kenichi Akaji、Yuzo Hayashi、Yoshiaki Kiso、Naohiro Kuriyama

  DOI：10.1021/jo981055a

  日期：1999.1.1

  Convergent synthesis of dolastatin 15 (1), a cytostatic depsipeptide isolated from the Indian Ocean sea hare, has been described. For construction of the backbone, a single-step condensation of peptide fragment 2 and pyrrolidone fragment 3 was successfully performed using 2-chloro-1,3-dimethyl-2-imidazolinium hexafluorophosphate (CIP) developed by us as an efficient coupling reagent. Coupling of an N-methylamino acid on solid support was first achieved using CTP for the efficient synthesis of peptide fragment 2. The effectiveness of CIP for the coupling of N-methylamino acids in solution and on solid support were clarified by the syntheses of model di- and tripeptides.
• Pettit, George R.; Herald, Delbert L.; Singh, Sheo Bux, Journal of the American Chemical Society, 1991, vol. 113, # 17, p. 6692 - 6693
  作者：Pettit, George R.、Herald, Delbert L.、Singh, Sheo Bux、Thornton, Timothy J.、Mullaney, Jeffrey T.

  DOI：——

  日期：——